Anatomy–guided interventional materials for precision pancreatic RNA delivery

Lipid nanoparticles (LNPs) have transformed RNA therapeutics, yet efficient delivery beyond the liver remains a major challenge. A recent study reported arginine–histidine–modified lipid nanoparticles (AH–LNPs) capable of achieving pancreas–selective RNA delivery through a previously unrecognized anatomical mechanism. In this Highlight, we summarize the key findings of this work and discuss their broader implications for precision interventional materials. AH–LNPs undergo protein–corona–induced size transformation following intraperitoneal administration, enabling a capsule–filter–mediated pancreatic–targeted (CAMP) mechanism that promotes preferential pancreatic accumulation. Subsequent enrichment of apolipoproteins within the protein corona facilitates very–low–density lipoprotein receptor–mediated pancreatic uptake (VMP), resulting in efficient cellular internalization, durable genome editing, and localized immunotherapy in pancreatic disease models. We further compare this strategy with representative pancreatic messenger RNA delivery platforms and discuss its conceptual distinction from conventional molecular targeting and selective organ–targeting approaches. Building upon these advances, we propose the concept of Anatomy–Guided Interventional Materials (AGIM), in which anatomical architecture, biological interfaces, administration routes, and material properties are integrated as programmable design elements to achieve precise therapeutic delivery. Finally, we discuss the translational challenges, future opportunities, and potential applications of anatomy–guided delivery strategies for RNA therapeutics targeting anatomically complex organs.